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MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors.
Hum Reprod. 2014 May; 29(5):978-88.HR

Abstract

STUDY QUESTION

Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions?

SUMMARY ANSWER

This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient and their correlation with the most important angiogenic and fibrinolytic factors. WHAT IS ALREADY KNOWN?: An important role for dysregulated miRNA expression in the pathogenesis of endometriosis is well documented. However, to the best of our knowledge, there are no reports of the relationship between angiogenic and fibrinolytic factors and miRNAs when endometrial tissue and different types of endometriotic lesions from the same patient are compared.

STUDY DESIGN, SIZE, DURATION

Case-control study that involved 51 women with endometriosis and 32 women without the disease (controls).

PARTICIPANTS/MATERIALS, SETTING, METHODS

The miRNA expression profiles were determined using the GeneChip miRNA 2.0 Affymetrix array platform, and the results were analysed using Partek Genomic Suite software. To validate the obtained results, 12 miRNAs differentially expressed were quantified by using miRCURY LNA™ Universal RT microRNA PCR. Levels of vascular endothelial growth factor (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) proteins were quantified by ELISA.

MAIN RESULTS AND THE ROLE OF CHANCE

Patient endometrial tissue showed significantly lower levels of miR-202-3p, miR-424-5p, miR-449b-3p and miR-556-3p, and higher levels of VEGF-A and uPA than healthy (control) endometrium. However, tissue affected by ovarian endometrioma showed significantly lower expression of miR-449b-3p than endometrium from both controls and patients, and higher levels of PAI-1 and the angiogenic inhibitor TSP-1. A significant inverse correlation between miR-424-5p and VEGF-A protein levels was observed in patient endometrium, and an inverse correlation between miR-449b-3p and TSP-1 protein levels was observed in ovarian endometrioma. Peritoneal implants had significantly higher levels of VEGF-A than ovarian endometrioma samples.

LIMITATIONS, REASONS FOR CAUTION

Functional studies are needed to confirm the specific targets of the miRNAs differently expressed.

WIDER IMPLICATIONS OF THE FINDINGS

Differences in miRNA levels could modulate the expression of VEGF-A and TSP-1, which may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in eutopic endometrium from patients might facilitate the implantation of endometrial cells at ectopic sites.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by research grants from ISCIII-FEDER (PI11/0091, Red RIC RD12/0042/0029), Consellería de Educación-Generalitat Valenciana (PROMETEO/2011/027), Beca de Investigación Fundación Dexeus para la Salud de la Mujer (2011/0469), and by Fundación Investigación Hospital La Fe (2011/211). A.B-B. has a Contrato Posdoctoral de Perfeccionamiento Sara Borrell-ISCIII (CD13/00005). J.M-A. has a predoctoral grant PFIS-ISCIII (FI12/00012). The authors have no conflicts of interest to declare.

Authors+Show Affiliations

Grupo de Hemostasia, Trombosis, Arteriosclerosis y Biología Vascular, Instituto Investigación Sanitaria Hospital La Fe (IIS La Fe), Valencia, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24608518

Citation

Braza-Boïls, Aitana, et al. "MicroRNA Expression Profile in Endometriosis: Its Relation to Angiogenesis and Fibrinolytic Factors." Human Reproduction (Oxford, England), vol. 29, no. 5, 2014, pp. 978-88.
Braza-Boïls A, Marí-Alexandre J, Gilabert J, et al. MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum Reprod. 2014;29(5):978-88.
Braza-Boïls, A., Marí-Alexandre, J., Gilabert, J., Sánchez-Izquierdo, D., España, F., Estellés, A., & Gilabert-Estellés, J. (2014). MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Human Reproduction (Oxford, England), 29(5), 978-88. https://doi.org/10.1093/humrep/deu019
Braza-Boïls A, et al. MicroRNA Expression Profile in Endometriosis: Its Relation to Angiogenesis and Fibrinolytic Factors. Hum Reprod. 2014;29(5):978-88. PubMed PMID: 24608518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. AU - Braza-Boïls,Aitana, AU - Marí-Alexandre,Josep, AU - Gilabert,Juan, AU - Sánchez-Izquierdo,Dolors, AU - España,Francisco, AU - Estellés,Amparo, AU - Gilabert-Estellés,Juan, Y1 - 2014/03/06/ PY - 2014/3/11/entrez PY - 2014/3/13/pubmed PY - 2014/12/17/medline KW - VEGF-A KW - angiogenesis KW - endometriosis KW - fibrinolysis KW - microRNA SP - 978 EP - 88 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 29 IS - 5 N2 - STUDY QUESTION: Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions? SUMMARY ANSWER: This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient and their correlation with the most important angiogenic and fibrinolytic factors. WHAT IS ALREADY KNOWN?: An important role for dysregulated miRNA expression in the pathogenesis of endometriosis is well documented. However, to the best of our knowledge, there are no reports of the relationship between angiogenic and fibrinolytic factors and miRNAs when endometrial tissue and different types of endometriotic lesions from the same patient are compared. STUDY DESIGN, SIZE, DURATION: Case-control study that involved 51 women with endometriosis and 32 women without the disease (controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: The miRNA expression profiles were determined using the GeneChip miRNA 2.0 Affymetrix array platform, and the results were analysed using Partek Genomic Suite software. To validate the obtained results, 12 miRNAs differentially expressed were quantified by using miRCURY LNA™ Universal RT microRNA PCR. Levels of vascular endothelial growth factor (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) proteins were quantified by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Patient endometrial tissue showed significantly lower levels of miR-202-3p, miR-424-5p, miR-449b-3p and miR-556-3p, and higher levels of VEGF-A and uPA than healthy (control) endometrium. However, tissue affected by ovarian endometrioma showed significantly lower expression of miR-449b-3p than endometrium from both controls and patients, and higher levels of PAI-1 and the angiogenic inhibitor TSP-1. A significant inverse correlation between miR-424-5p and VEGF-A protein levels was observed in patient endometrium, and an inverse correlation between miR-449b-3p and TSP-1 protein levels was observed in ovarian endometrioma. Peritoneal implants had significantly higher levels of VEGF-A than ovarian endometrioma samples. LIMITATIONS, REASONS FOR CAUTION: Functional studies are needed to confirm the specific targets of the miRNAs differently expressed. WIDER IMPLICATIONS OF THE FINDINGS: Differences in miRNA levels could modulate the expression of VEGF-A and TSP-1, which may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in eutopic endometrium from patients might facilitate the implantation of endometrial cells at ectopic sites. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research grants from ISCIII-FEDER (PI11/0091, Red RIC RD12/0042/0029), Consellería de Educación-Generalitat Valenciana (PROMETEO/2011/027), Beca de Investigación Fundación Dexeus para la Salud de la Mujer (2011/0469), and by Fundación Investigación Hospital La Fe (2011/211). A.B-B. has a Contrato Posdoctoral de Perfeccionamiento Sara Borrell-ISCIII (CD13/00005). J.M-A. has a predoctoral grant PFIS-ISCIII (FI12/00012). The authors have no conflicts of interest to declare. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/24608518/MicroRNA_expression_profile_in_endometriosis:_its_relation_to_angiogenesis_and_fibrinolytic_factors_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/deu019 DB - PRIME DP - Unbound Medicine ER -